Insights into the antiosteoporotic mechanism of the soy‐derived isoflavone genistein: Modulation of the Wnt/beta‐catenin signaling

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Insights into the antiosteoporotic mechanism of the soy-derived isoflavone genistein: Modulation of the Wnt/beta-catenin signaling

Glucocorticoid-induced osteoporosis (GIO) reduces bone formation, osteoblasts differentiation and function, and accelerates osteoblast and osteocyte apoptosis. Genistein induces bone remodeling through Wnt/β-catenin pathway activation in osteoblast and osteocytes. Genistein could represent an interesting new therapeutic approach for the management of GIO patients.


Abstract

Bone remodeling is a process that involves osteoblasts, osteoclasts, and osteocytes, and different intracellular signaling, such as the canonical Wnt/β-catenin pathway. Dysregulations of this pathway may also occur during secondary osteoporosis, as in the case of glucocorticoid-induced osteoporosis (GIO), which accelerates osteoblast and osteocyte apoptosis by reducing bone formation, osteoblast differentiation and function, accelerates in turn osteoblast, and osteocyte apoptosis. Genistein is a soy-derived nutrient belonging to the class of isoflavones that reduces bone loss in osteopenic menopausal women, inhibiting bone resorption; however, genistein may also favor bone formation. The aim of this study was to investigate whether estrogen receptor stimulation by genistein might promote osteoblast and osteocyte function during glucocorticoid challenge. Primary osteoblasts, collected from C57BL6/J mice, and MLO-A5 osteocyte cell line were used to reproduce an in vitro model of GIO by adding dexamethasone (1 μM) for 24 h. Cells were then treated with genistein for 24 h and quantitative Polymerase Chain Reaction (qPCR) and western blot were performed to study whether genistein activated the Wnt/β-catenin pathway. Dexamethasone challenge reduced bone formation in primary osteoblasts and bone mineralization in osteocytes; moreover, canonical Wnt/β-catenin pathway was reduced following incubation with dexamethasone in both osteoblasts and osteocytes. Genistein reverted these changes and this effect was mediated by both estrogen receptors α and β. These data suggest that genistein could induce bone remodeling through Wnt/β-catenin pathway activation.

Effects of household composition on infant feeding and mother–infant health in northern Kenya

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Abstract

Background

Households with alloparents, individuals other than the mother who care for an infant, can shift members' roles and affect mother–infant health.

Aims

To investigate how household composition relates to infant feeding and infectious disease risk in mother–infant dyads, the team utilized data from breastfeeding dyads (n 208) surveyed during a prolonged drought and food scarcity in northern Kenya.

Methods

Households were classified by the presence/absence of potential alloparents, distinguishing non-siblings and siblings of the infant. Regression models for breastfeeding frequency, complementary feeding status, and recent infections (n 83) evaluated these outcomes' associations with household type while accounting for food insecurity, adjusted for infant age, infant sex, and maternal age.

Results

Household type was unassociated with breastfeeding frequency, but the presence of non-sibling alloparents interacted with food insecurity, predicting increasing breastfeeding frequency as food insecurity intensified among dyads living with non-sibling alloparents. Households with non-sibling alloparents were also inversely associated with complementary feeding but had no association with infection. Households with siblings were inversely associated with (protective against) infant and maternal infection.

Conclusion

Further research is needed to understand the interactive influence of household social and food ecologies on mother–infant diet and health under diverse cultural rules and norms for alloparenting.

Recent advances in understanding the role of the skin microbiome in the treatment of atopic dermatitis

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Abstract

The skin is the largest organ in the human body, and histologically consists of the epidermis, dermis and subcutaneous tissue. Humans maintain a cooperative symbiotic relationship with their skin microbiota, a complex community of bacteria, fungi and viruses that live on the surface of the skin, and which act as a barrier to protect the body from the inside and outside. The skin is a ‘habitat’ and vast ‘ecosystem’ inhabited by countless microbes; as such, relationships have been forged through millions of years of coevolution. It is not surprising then that microbes are key participants in shaping and maintaining essential physiological processes. In addition to maintaining barrier function, the unique symbiotic microbiota that colonizes the skin increases the immune response and provides protection against pathogenic microbes. This review examines our current understanding of skin microbes in shaping and enhancing the skin barrier, as well as skin microbiome–host interactions and their roles in skin diseases, such as atopic dermatitis (AD). We also report on the current status of AD therapeutic drugs that target the skin microbiome, related research on current therapeutic strategies, and the limitations and future considerations of skin microbiome research. In particular, as a future strategy, we discuss the need for a skin-on-a-chip-based microphysiological system research model amenable to biomimetic in vitro studies and human skin equivalent models, including skin appendages.

Better understanding CD8<sup>+</sup> T cells in cancer and viral infections

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Nature Immunology, Published online: 28 September 2023; doi:10.1038/s41590-023-01630-x

The first conference on ‘Infection and Immunity’ was organized by the Institute for Basic Science and Korean Association of Immunologists and held in Daejeon, South Korea, from 12 to 14 July 2023. The conference focused on the biology of CD8+ T cells in the context of viral disease and cancer.

Directed evolution unlocks oxygen reactivity for a nicotine-degrading flavoenzyme

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Nature Chemical Biology, Published online: 28 September 2023; doi:10.1038/s41589-023-01426-y

The flavoenzyme nicotine oxidoreductase degrades nicotine in the bloodstream. Now, genetic selection in bacteria has been used to improve the catalytic performance of nicotine oxidoreductase, isolating variants with increased O2 reactivity that were more effective at degrading nicotine in the blood of rats.

Sentinel cells programmed to respond to environmental DNA including human sequences

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Nature Chemical Biology, Published online: 28 September 2023; doi:10.1038/s41589-023-01431-1

Nou et al. engineered Bacillus subtilis cells into a living sentinel system, which can take up environmental DNA and fluoresce when a matching sequence is detected. This system enables recording of SNPs for facial features and has broad applications spanning forensics to agriculture.

Should sons breed independently or help? Local relatedness matters

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Should sons breed independently or help? Local relatedness matters

Why do some younger individuals breed themselves, whereas other counterparts help? This question is addressed using 15 years of data from a Tibetan bird. The finding—kin neighbourhoods facilitate younger males to acquire a territory and breed independently—explains how the kin-based, facultative cooperative societies form in vertebrates. (Illustration: Y. Chen; Photo: D. Ke).


Abstract

In cooperatively breeding birds, why do some individuals breed independently but others have to help at home? This question has been rarely addressed despite its fundamental importance for understanding the evolution of social cooperation. We address it using 15 years of data from Tibetan ground tits Pseudopodoces humilis where helpers consist of younger males. Since whether younger males successfully breed depends critically on their chances to occupy territories nearby home, our analytic strategy is to identify the determinants of individual differences in gaining territory ownership among these ready-to-breed males. Across widowed, last-year helper and yearling males, an age advantage was evident in inheriting resident territories, occupying adjacent vacancies and budding off part of adjacent territories, which left some last-year helpers and most yearling males to take the latter two routes. These males were more likely to acquire a territory if they were genetically related to the previous or current territory owners; otherwise they remained on natal territories as helpers. The relatedness effect can arise from the prior residence advantage established in the preceding winter when younger males followed their parents to perform kin-directed off-territory forays. Our research highlights the key role of local kinship in determining younger males' territory acquisition and thus their fate in terms of independent reproduction versus help. This finding provides insight into the formation of kin-based, facultative cooperative societies prevailing among vertebrates.

摘要

在合作繁殖鸟类中，为什么一些性成熟的个体独立繁殖，而其它被迫留家帮助?尽管这一问题对于理解社会进化至关重要，但迄今没有得到充分回答。 我们使用来自青藏高原特有物种地山雀15年的野外数据，企图回答这一问题。研究种群中，帮助者都是年轻的雄性。这些个体的繁殖成功，取决于其是否能在家族领域附近获得自己的领域。因此，我们的分析策略就是识别决定繁殖雄性个体获得领域的关键因素。 在继承领域、占据相邻空缺领域和瓜分相邻领域方面，丧偶雄性、上年帮助者和一龄雄性的优势依次降低。这使得一些上年帮助者和大多数一龄雄性不得不采取后两种获得领域的途径。我们发现，如果这些年轻雄性与相邻空缺的前任、或被挤占领域的现任拥有者为亲属，他们就更可能获得领域而独立繁殖；否则便沦为留家的帮助者。这种亲属效应来自冬季年轻雄性跟随父亲频繁访问相邻亲属领域而预先建立的对潜在未来领域的熟悉性。 我们的研究凸显了邻里亲缘关系在决定年轻雄性能否获得领域、进而独立繁殖或成为帮助者的关键作用。该发现增进了人们对普遍存在于脊椎动物中以亲缘关系为基础的兼性合作社会形成机制的理解。

Development and validation of machine learning model for predicting treatment responders in patients with primary biliary cholangitis

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Development and validation of machine learning model for predicting treatment responders in patients with primary biliary cholangitis


Abstract

Aims

Ursodeoxycholic acid is the first-line treatment for primary biliary cholangitis, and treatment response is one of the factors predicting the outcome. To prescribe alternative therapies, clinicians might need additional information before deciphering the treatment response to ursodeoxycholic acid, contributing to a better patient prognosis. In this study, we developed and validated machine learning (ML) algorithms to predict treatment responses using pretreatment data.

Methods

This multicenter cohort study included collecting datasets from two data samples. Data 1 included 245 patients from 18 hospitals for ML development, and was divided into (i) training and (ii) development sets. Data 2 (iii: test set) included 51 patients from our hospital for validation. An extreme gradient boosted tree predicted the treatment response in the ML model. The area under the curve was used to evaluate the efficacy of the algorithm.

Results

Data 1 showed that patients complying with the Paris II treatment response had significantly lower serum alkaline phosphatase and total bilirubin levels than those who did not respond. Three factors, total bilirubin, total protein, and alanine aminotransferase levels were selected as essential variables for prediction. Data 2 showed that patients complying with the Paris II criteria had significantly high prothrombin time and low total bilirubin levels. The area under the curve of extreme gradient boosted tree was good for (ii) (0.811) and (iii) (0.856).

Conclusions

We demonstrated the efficacy of ML in predicting the treatment response for patients with primary biliary cholangitis. Early identification of cases requiring additional treatment with our novel ML model may improve prognosis.

Cost‐effectiveness analysis of hepatitis E vaccination strategies among patients with chronic hepatitis B in China

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Cost-effectiveness analysis of hepatitis E vaccination strategies among patients with chronic hepatitis B in China

The cost-effectiveness of hepatitis E vaccination for patients with chronic hepatitis B (CHB) is unclear. We developed a decision tree–Markov model to assess the cost-effectiveness of three hepatitis E vaccination strategies among these patients. We found that the disease burden in CHB patients superinfected with hepatitis E virus is relatively heavy in China, and the screening-based hepatitis E vaccination strategy for CHB patients is the most cost-effective option.


Abstract

Aim

This study aimed to evaluate the cost-effectiveness of hepatitis E vaccination strategies in chronic hepatitis B (CHB) patients.

Methods

Based on the societal perspective, the cost-effectiveness of three hepatitis E vaccination strategies—vaccination without screening, screening-based vaccination, and no vaccination—among CHB patients was evaluated using a decision tree–Markov model, and incremental cost-effectiveness ratios (ICERs) were calculated. Values for treatment costs and health utilities were estimated from a prior investigation on disease burden, and values for transition probabilities and vaccination-related costs were obtained from previous studies and government agencies. Sensitivity analyses were undertaken for assessing model uncertainties.

Results

It was estimated that CHB patients superinfected with hepatitis E virus (HEV) incurred significantly longer disease course, higher economic burden, and more health loss compared to those with HEV infection alone (all p < 0.05). The ICERs of vaccination without screening and screening-based vaccination compared to no vaccination were 41,843.01 yuan/quality-adjusted life year (QALY) and 29,147.32 yuan/QALY, respectively, both lower than China's per-capita gross domestic product (GDP) in 2018. The screening-based vaccination reduced the cost and gained more QALYs than vaccination without screening. One-way sensitivity analyses revealed that vaccine price, vaccine protection rate, and decay rate of vaccine protection had the greatest impact on the cost-effectiveness analysis. Probabilistic sensitivity analyses confirmed the base-case results, and if the willingness-to-pay value reached per-capita GDP, the probability that screening-based vaccination would be cost-effective was approaching 100%.

Conclusions

The disease burden in CHB patients superinfected with HEV is relatively heavy in China, and the screening-based hepatitis E vaccination strategy for CHB patients is the most cost-effective option.